DIETARY GUIDANCE -- But the study said... it might as well have been made up!

We all see new studies about diet and weight loss all the time (well, that was until Ozempic and Mounjaro came out).  And it turns out that the data is so flawed that you might as well have made it up yourself!

There are two main types of diet-related studies, at least as far as data collection goes.  One type we’re not going to discuss involves locking someone up in a ward and strictly limiting everything so as to control as many variables as possible.  Super expensive, and rarely, if ever done anymore.  The two types I’m talking about are food survey questionnaires, and food journals.  

Food journals ask patients to report intake of specific foods and usually their macronutrients – how much fat, carbs and protein they consume.  Judgements are then made as to the categories patients might fall into.  

Food survey questionnaires ask more general questions, several times over a specific time period, asking patients to recall what they ate and how much.

Let’s take the food recall survey first – most people can’t remember what they had for breakfast, no less how many potatoes they ate over the last two weeks, two months or two years!  Needless to say, some inherent self-reporting bias is expected.  But it seems that that bias may approach error rates of 50%!

You might think food journals are better.  But when patients were asked to follow specific diet guidelines (low carb or low fat, for example), the reports of following guidelines differed from reality by 77 – 96%!!

If most of the reports are in error, would it be safer to assume the exact opposite of the conclusions being reported?  OKAY,  maybe that’s not the best idea, but it does lend credence to the notion that not every piece of advice or guidance offered is worth paying attention to.  

Having someone who knows you and your issues and needs might just be better than following the herd…just saying.

FROM MEDSCAPE INTERNAL MEDICINE / BY
YONI FREEDHOFF, MD

Disappointing Outcomes Show Futility of Weight Loss Studies

Self-reported diet adherence may be as useful and accurate as self-reported height and weight, where people somehow end up being taller and lighter than they are. At least that’s what the findings from a recent study would suggest. The study, “Are People Consuming the Diets They Say They Are? Self-Reported vs Estimated Adherence to Low-Carbohydrate and Low-Fat Diets: National Health and Nutrition Examination Survey, 2007-2018,” published in the Journal of the Academy of Nutrition and Dietetics, compared self-reported diet adherence among low-carb and low-fat dieters with two separate 24-hour recalls conducted with those same individuals.

The findings were striking. Of self-reported low-carb dieters — a diet with a generally higher degree of implementation difficulty — when compared with their 24-hour recall data, 95.9% were not meeting the low-carb threshold of consuming less than 26% of energy from carbohydrates. Of the self-reported low-fat dieters, though certainly better, 77% were found not to be consuming less than 30% of energy from fats.

The implications of this are plain. Studies on free-range, non–metabolic ward dieters that base their conclusions on self-identified diet adherence should be evaluated with great skepticism. 

And it’s not just self-identified diet adherence that challenges diet study conclusions. We should also question the reliability of food frequency questionnaires (FFQs) — especially in longer-term studies, given that the longer the study, the less likely the extrapolation of sometimes even singular FFQ measurements to reflect even a decade of ongoing dietary intake patterns as if they never change. This effect is compounded by inaccuracy among food self-reporters, as demonstrated by the recent confirmatory evidence that overall, we’re terrible food historians. The study, “Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables the Detection of Erroneous Self-Reported Energy Intake,” utilizing objective doubly labeled water to evaluate the accuracy of subjective self-reports of energy intake, found that roughly 50% of people’s reported intakes didn’t mirror their measured total energy expenditure (TEE)s! The study also found that, when looking specifically at people with obesity (the subjects of most diet studies), their misreporting was associated with underreporting energy intake, overreporting protein intake, and underreporting fat intake — even further skewing our ability to interpret diet impact studies.

Another generally unspoken challenge to the evaluation of diet studies is that most — including the most thoughtfully conducted and measured — tend to be studied in the context of evaluating either a commercial or a medically supervised and administered dieting program. The challenge therein has to do with the fact that dietary counseling and support is a service and not a product, and as a service, its outcomes will be deeply influenced by the skills of those administering it. What that means is it’s impossible to disentangle the skills, or lack thereof, of the study or program’s administrators from the ease or enjoyability of the diet being studied and from the outcomes of its participants. Terrific clinicians are more likely than terrible clinicians to inspire greater changes and adherence. And so, a study on a particular commercial diet program’s outcome is at best extrapolatable only to the centers and support staff who administered it. 

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Worse, especially for long-standing commercial dieting programs, is that the programs change over time. For instance, Weight Watchers, just since 2000, has implemented at least six major changes to its plan. How then to evaluate studies both prior to the 2000s and since the 2000s, given the differences in the programs?

But again, as I’ve been saying for quite a while now, regardless of the diet or program studied, despite decades of efforts and initiatives, there has yet to be a scalable, reproducible, years-long program that delivers clinically meaningful long-term weight loss. What are we even studying when we’re evaluating diets? And who are we benefiting? Because it would appear we’re not actually studying the diets we’re reporting we’re studying, and are we really benefiting anyone given that no diet has proven itself to be superior to any other in terms of leading to long-term success? 

From the individual patient’s perspective, the diet they should be striving for is the healthiest one that they can actually enjoy. If not enjoyable, the likelihood of it being sustained long term is low to nonexistent. And one person’s best diet is another person’s worst. Which is why when looking at waterfall plots of weight loss of individuals on a particular program or diet, you’re likely to see some patients with dramatic losses vs some with even weight gains, and then a whole bunch in a nonexciting middle (assuming excitement is determined by amount lost).

Moving forward, I’m hoping for fewer weight loss diet studies consequent to both the lack of signal in diet studies to date demonstrating reproducible utility, coupled with the undeniable superiority of medication in conferring long-term, clinically meaningful losses. What remains to be seen is whether in the context of people taking obesity medications, there’s a best diet for same, and where adherence is amplified consequent to medication-induced decreases in hunger, cravings, and fullness, leaving individuals with a far greater chance of sticking with their chosen effort.

Source: https://www.medscape.com/viewarticle/disap...

Does your Blood Pressure medication give you CANCER?

Thiazide diuretics are probably the most prescribed blood pressure medications in the world.  This study reminds us that they also raise of the risk of skin cancer, and in some cases BY A LOT!  If you have had skin cancer or the family has elevated risk, you might want to rethink this medication.

FROM MEDSCAPE INTERNAL MEDICINE / BY HAREEN SEERHA; DOUGLAS S. PAAUW, MD


Should We Be Concerned About These BP Medications Causing Cancer?

A 50-year-old White woman presents for evaluation of a new skin lesion on her face that has been present for the past 4 months. Biopsy reveals a squamous cell carcinoma (SCC). She previously had an SCC removed from her left arm 2 years ago. She is currently taking lisinopril, amlodipine, hydrochlorothiazide, omeprazole, turmeric, and sertraline.

Which medication would it be appropriate to replace? 
    A) Lisinopril
    B) Amlodipine
    C) Hydrochlorothiazide
    D) Omeprazole
    E) Sertraline

We think replacing her hydrochlorothiazide would be appropriate, given that she has developed two SCCs at a young age.

Thiazides

As we continue to prescribe thiazides for hypertensive patients, it may be worthwhile to initiate and discuss skin protection alongside treatment. The photosensitizing properties of thiazide diuretics have raised concerns that these treatments may increase the risk for skin cancer.

A meta-analysis conducted by Shin and colleagues analyzed nine observational studies to investigate the association between thiazide use and skin cancer. Thiazide use was significantly associated with small SCCs with an adjusted odds ratio (AOR) of 1.86 (95% CI, 1.23-2.80). Thiazide use had marginally increased associations with basal cell carcinoma (BCC) (AOR, 1.19; 95% CI, 1.02-1.38) and malignant melanoma (AOR, 1.14; 95% CI, 1.01-1.29). 

Pedersen and colleagues studied a Danish database and found that high use of hydrochlorothiazide (> 50,000 mg) was associated with ORs of 1.29 (95% CI, 1.23-1.35) for BCC and 3.98 (95% CI, 3.68-4.31) for SCC. They found that there was a dose-response effect; the highest cumulative dose category (> 200,000 mg hydrochlorothiazide) had ORs of 1.54 (95% CI, 1.38-1.71) for BCC and 7.38 (95% CI, 6.32-8.60) for SCC.

Rahamimov and associates  looked at the risk in kidney transplant patients of developing skin cancer on thiazide diuretic treatment. As we know, immunosuppression increases the risk of developing cancer in general; however, there is concern that this risk will increase with a concurrent thiazide prescription. Rahamimov’s group conducted a retrospective analysis of 520 kidney transplant recipients on immunosuppressants and thiazides in 2010-2015. Exposure to thiazides 3 years after transplant was associated with an increased risk for skin cancer (P =.004), particularly nonmelanoma skin cancer.

Rahamimov's group suggests establishing dermatology care for kidney transplant patients receiving thiazide treatments in areas with high ultraviolet light. It is also important to assess skin malignancy risk factors, do thorough skin exams before and while prescribing thiazides to patients, and educate patients about ultraviolet light protection. This is especially important for patients with light complexions, as there did not appear to be an increased risk in a large study of an Asian population in Taiwan. 

It makes sense to avoid thiazide diuretics, if possible, in the highest-risk patients — those with multiple previous skin cancers and those who are chronically immunosuppressed. 

ACE Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors have been revolutionary for patients with cardiovascular disease; however, recent studies have raised concerns over whether this mortality-reducing drug increases the risk for lung cancer. 

A study published by the American Heart Association used a nested case-control design to assess lung cancer associated with ACE inhibitor use compared with angiotensin II receptor blocker (ARB) use. The researchers conducted a population-wide study using Danish national and administrative registries from 2000 to 2015. They found that while low cumulative ACE inhibitor doses showed neutral associations with lung cancer, high cumulative doses were associated with increased odds of lung cancer. 

A meta-analysis conducted by Wu and colleagues analyzed records from 11 studies to assess the association between ACE inhibitor use and lung cancer. The researchers accounted for factors such as smoking, race, and age. They concluded that ACE inhibitors are a relevant factor in lung carcinogenesis and pose a higher risk compared with ARBs, especially among Asian populations. Another study within this meta-analysis showed that statins may mitigate this association, reducing the risk when a statin and an ACE inhibitor are prescribed together. 

In recent years, there has been increasing evidence supporting the connection between ACE inhibitors and the development of lung cancer. ACE inhibitors result in the accumulation of bradykinin and substance P. Not only does this often cause a notorious cough, but these inflammation markers are associated with tumor proliferation and angiogenesis. However, more randomized controlled trials are needed to determine the causal association between ACE inhibitors and lung cancer. ARBs, although currently second-line drugs, do not cause accumulation of bradykinin. Perhaps it is time to rethink our approach to cardiovascular disease treatments.

Pearls

  • Considering the risk that thiazides and ACE inhibitors can pose for developing malignancies, it is important to screen patients for risk factors prior to prescribing treatment.

  • Although skin exams can be tedious and patients may push back on sunscreen use, these conversations may be important for those taking thiazides; avoidance of thiazides in high-risk patients may be warranted.

  • Perhaps it is time to consider ARBs over ACE inhibitors.

Source: https://www.medscape.com/viewarticle/shoul...

Wildfires can "burn" you over months

We are back in the haze.  Wildfires in Canada are wafting smoke into our area.  You see it in the haze, the reddish hues around the sun, especially around sunrise and sunset.  And air quality alerts are on the media outlets.  

Turns out that elevated levels of these particles carry risks.  It’s been known for decades that air pollution (small particulates) raise the risk of lung diseases, heart attacks, even strokes.  Now there’s an article that shows that the wildfire smoke doesn’t just raise your risk in the short term, but that risk carries forward for at least 3 months.  

If you are one of the “sensitive” groups – lung problems, heart problems – then try to stay inside and keep the windows closed when there’s an air quality alert.  It might just save your life.

FROM EPIDEMIOLOGY / BY WEI, YAGUANG; CASTRO, EDGAR; YIN, KANHUA; SHTEIN, ALEXANDRA; VU, BRYAN N.; DANESH YAZDI, MAHDIEH; LI, LONGXIANG; LIU, YUXI; PERALTA, ADJANI A.; SCHWARTZ, JOEL D.

Abstract

Background: 

Wildfire activity in the US has increased substantially in recent decades. Smoke PM2.5, a primary wildfire emission, can spike for months after a wildfire begins, yet large-scale evidence of its health effects remains limited.

Methods: 

We obtained hospitalization records for the residents of 15 states between 2006–2016 from the State Inpatient Databases. We used existing daily smoke PM2.5 estimations at 10-km2 grid cells across the contiguous US, and aggregated them to ZIP codes to match the spatial resolution of hospitalization records. We extended traditional case–crossover design, a self-controlled design originally developed for studying acute effects, to examine associations between 3-month average exposure to smoke PM2.5 and hospitalization risks for a comprehensive range of cardiovascular (ischemic heart disease, cerebrovascular disease, heart failure, arrhythmia, hypertension, other cardiovascular diseases) and respiratory diseases (acute respiratory infections, pneumonia, COPD, asthma, other respiratory diseases).

Results: 

We found that 3-month exposure to smoke PM2.5 was associated or marginally associated with increased hospitalization risks for most cardiorespiratory diseases. Hypertension showed the greatest susceptibility, with the highest hospitalization risk associated with 0.1 µg/m3 increase in 3-month smoke PM2.5 exposure (relative risk: 1.0051; 95% confidence interval: 1.0035, 1.0067). Results for single-month lagged exposures suggested that estimated effects persisted up to 3 months after exposure. Subgroup analyses estimated larger effects in neighborhoods with higher deprivation level or more vegetation, as well as among ever-smokers.

Conclusions: 

Our findings provided unique insights into medium-term cardiorespiratory effects of smoke PM2.5, which can persist for months, even after a wildfire has ended.

Source: https://journals.lww.com/epidem/abstract/9...

More Floss, Less Strokes (not talking teeth)

If you go to feldmed.com, you’ll see a gnarly picture of a guy brushing his teeth.  We talk about how poor oral health leads to heart attacks.  Well, here’s another variation on the theme – regular Flossing reduces Strokes.  A regular flosser was someone who reported flossing once a week or more.  I suppose not surprisingly, flosser had somewhat lower risks of hypertension and diabetes.  They also had better gums, but their good cholesterol levels were higher, too,

What was a little surprising was that strokes were lower, but it seemed that the association was tied to less atrial fibrillation, which is an increasingly prevalent condition.  More flossing also meant a greater reduction.  

While not definitive, seems like I could include flossing in a routine…

FROM MEDSCAPE IM / BY PAULINE ANDERSON

Regular Flossing Tied to Reduced Ischemic Stroke Risk

Regular dental flossing is linked to a lower risk for ischemic stroke, primarily by reducing systemic inflammation, which can lead to atrial fibrillation (AF) increasing the likelihood of a cardioembolic event, new research suggested.

The reduced risk is independent of oral care such as regular teeth brushing and visits to the dentist, the research showed.

“We knew that flossing regularly will lower the body’s level of inflammation, and the level of oral infection, but now, based on this study, we know it will reduce the rate of stroke, atrial fibrillation, and cardioembolic stroke,” study investigator Souvik Sen, MD, professor and chair, Department of Neurology, University of South Carolina School of Medicine Columbia, told Medscape Medical News.

Flossing is an affordable health measure that could be “a very good primary prevention strategy,” especially in rural areas where individuals have less access to dental care, said Sen.

The findings were presented on February 5 at the International Stroke Conference (ISC) 2025.

Unclear Link 

Recent research has shown flossing lowers the risk for myocardial infarction. When it comes to stroke and AF, previous studies showed an association with oral infection, but the impact of preventative oral care such as dental flossing was unclear.

The study included 6278 participants in the Atherosclerosis Risk in Communities (ARIC) study with no history of stroke or AF (mean age, 62 years). The ongoing ARIC study began in 1987 in four US counties.

On visit four (1996-98), participants completed a structured questionnaire on oral hygiene. Respondents were asked if, and how often, they flossed. At least once a week was considered regular flossing. They were also asked how often they visited a dentist. Once a year was considered regular dental care. Participants also reported vascular risk factors and socio-demographic features.

Participants were categorized as flossers (n = 4092) and nonflossers (n = 2186).There were more women in the flosser group than in the nonflosser group and more men in the nonflosser group than in the flosser group. In addition, the percentage of African Americans was almost twice as high in the nonflossing group than in the flossing group.

Flossers had fewer relevant cardiovascular risk factors. For example, 31.5% of flossers had hypertension and 11.7% had diabetes vs 36.3% and 16.1%, respectively, of the non-flossers.

Flossers also had significantly higher high-density lipoprotein levels and significantly lower levels of periodontal disease and dental caries.

‘A Big Finding’

Participants had regular follow-up for > 25 years. If a stroke was reported, this was followed up through medical records. An independent neurologist verified the stroke and determined the type, said Sen.

During the follow-up period, 434 strokes were identified. Of these 146 were thrombotic, 102 cardioembolic, and 95 lacunar subtypes.

Researchers controlled for a number of factors including age, gender, race, obesity, blood pressure, diabetes, education level, smoking, regular brushing, and regular visits to the dentist.

The investigators found that flossing was significantly associated with a lower risk for ischemic stroke (adjusted hazard ratio [HR], 0.79; 95% CI, 0.64-0.97), cardioembolic stroke subtype (adjusted HR, 0.56; 95 CI, 0.36-0.86) and AF (adjusted HR, 0.88; 95% CI, 0.78-1.00).

The analysis suggested the stroke risk reduction was “primarily driven” by fewer cardioembolic strokes, “which is possibly linked to a reduced rate of atrial fibrillation,” said Sen.

“That’s a big finding because atrial fibrillation seems to be increasing and more and more people are having a stroke from atrial fibrillation. I think we haven’t focused enough on how to prevent atrial fibrillation in the first place because that leads to bigger and more devastating strokes,” Sen added.

Additional Benefit With Flossing

He noted that the results are independent of tooth brushing and regular visits to the dentist. “The results are above and beyond taking care of your oral health and suggest that flossing has an additional impact.” 

Flossing removes food particles or plaque stuck between teeth and cleans the gums, and does this better than brushing can, explained Sen. Plaque can cause gum disease and tooth decay, which can lead to inflammation, he added.

“Inflammation has been tied to hardening of the blood vessels, or atherosclerosis, and that leads to heart attack and based on our study, to stroke and irregular heartbeat.” 

Flossing was not significantly associated with thrombotic stroke (adjusted HR, 0.91; 95% CI, 0.63-1.32) or lacunar stroke (adjusted HR, 1.14; 95% CI, 0.54-1.88). There was a significant dose-effect between the frequency of flossing and the reduction in incident ischemic stroke, noted Sen.

Commenting on the research on behalf of the American Heart Association/American Stroke Association, Daniel T. Lackland, DrPH, FAHA, professor of epidemiology and director, Division of Translational Neurosciences and Population Studies, Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, said the study addresses whether “there’s some part of dental hygiene” that could reduce the risk for stroke.

The study added new information that suggests “perhaps dental flossing is associated with a lower risk of cardiovascular disease,” said Lackland, who is also an American Heart Association Epidemiology and Stroke Council member.

Source: https://www.medscape.com/viewarticle/regul...

If you wait, the kids will get bigger.... And so will their problems

This study falls under the “Really, Sherlock?” category.  Sometimes proving something for the sake of proving seems wasteful to me, and I’m being kind.

If an obese kid is given obesity treatment… wait for it…. And they respond well, they will have a reduced risk of obesity-related events as young adults.  That means if you can get kids to lose weight, their risks of diabetes, high cholesterol, needing bariatric surgery, high blood pressure or even dying will be cut in half or better.  Is anyone surprised by this??

I guess the point was that spending the money early actually paid for itself – it is, after all, all about the money.

FROM MEDPAGE TODAY / BY JENNIFER HENDERSON

Good Response to Obesity Treatment in Childhood Improved Outcomes Down the Line

Findings represent "a hopeful message that early intervention truly matters," researcher says.

Beneficial pediatric obesity treatment response was associated with a reduced risk of obesity-related events in young adults, a nationwide prospective cohort study in Sweden showed.

Compared with poor response, good response to obesity treatment was associated with lower risk of type 2 diabetes (adjusted HR [aHR] 0.42, 95% CI 0.23-0.77), dyslipidemia (aHR 0.31, 95% CI 0.13-0.75), and bariatric surgery (aHR 0.42, 95% CI 0.30-0.58), reported Emilia Hagman, PhD, of the Karolinska Institute in Sweden, and colleagues.

Obesity remission showed similar reduced risks, as well as reduced risk of hypertension (aHR 0.40, 95% CI 0.24-0.65). Good response in obesity treatment or obesity remission was associated with a reduced risk of mortality (aHR 0.12, 95% CI 0.03-0.46), though treatment response was not associated with reduced risk for depression or anxiety, they noted in JAMA Pediatrics.

"The long-term effects of treating obesity in childhood were largely unknown," Hagman told MedPage Today in an email. "Many people believe that because maintaining weight loss is so challenging, early treatment might not make a real difference in reducing the risk of serious health problems like type 2 diabetes, high blood pressure, or heart disease later in life. Our research helps answer this critical question and shows the importance of addressing obesity early."

Evidence-based treatment options for childhood obesity -- mainly behavioral lifestyle modification -- have been available for more than 15 years in Sweden, Hagman and colleagues noted.

"I found it especially encouraging that lifestyle therapy for obesity in childhood can have a lasting impact well into adulthood," Hagman told MedPage Today. "While there are very positive outcomes from weight-loss surgery, this study shows that responding to early lifestyle therapy can also lead to long-term benefits, even up to 30 years of age. It's a hopeful message that early intervention truly matters."

In an editorial accompanying the study, Leonard Epstein, PhD, of the University at Buffalo in New York, and colleagues, pointed out, however, that the type of treatment was not presented, which is important as different types of treatment can impact outcomes differently.

Also, "the broad definition of treatment duration does not provide an indication of intensity, frequency, or number of treatments," Epstein and colleagues wrote. And additional data on parental and sibling obesity "would be valuable to assess the impact of the pediatric treatment implemented on the state of transgenerational obesity within a family," they added.

Still, the study by Hagman and colleagues "demonstrates for the first time, to our knowledge, the impact of pediatric treatment for obesity on young adult cardiometabolic disease, bariatric surgery, and mortality," they wrote. "These data will be useful to consider criteria for clinical effectiveness of treatment, as well as pointing out limitations in our current approaches to treatment of pediatric obesity."

Ultimately, Hagman said she believes "the long-term goal of treating childhood obesity should go beyond improving lifestyle habits and quality of life -- it should also focus on reducing the degree of obesity itself."

"While well-being is incredibly important, this research shows that failing to achieve weight loss can lead to serious health problems, like type 2 diabetes, early in life," Hagman added. "This highlights the need for clinicians to prioritize effective weight management in their care plans."

For their study, Hagman and colleagues examined children and adolescents with obesity within The Swedish Childhood Obesity Treatment Register (BORIS) along with general population comparators. Study participants were 6 to 17 years of age who received at least 1 year of obesity treatment; comparators were matched on a ratio of 1:5 on sex, year of birth, and geographical area.

Baseline data were collected between 1996 and 2019, with formal analyses conducted in 2023. Outcomes were assessed for individuals 18 to 30 years of age between 2005 and 2020.

Of 6,713 individuals included in the study, 56% were male. The median age at obesity treatment initiation was 12.1 years, and the median treatment duration was 3 years.

Limitations included that the National Patient Register does not encompass non-specialized medical care, such as primary care, and though many conditions in the study are usually managed with pharmacotherapy, it could not be ruled out that certain conditions might have been managed exclusively with lifestyle modifications. Additionally, because obesity-related comorbidities often occur asymptomatically, this could have impeded an accurate assessment of true incidence. Also, even with substantial healthcare reimbursement in Sweden, selection bias was a concern.

Source: https://www.medpagetoday.com/pediatrics/ge...

The Neuroscience of Bubbles -- they do more than tickle your nose

Gabriel Lepousez is a neuroscientist working in perception and memory and asked the question” “Why does your brain love bubbles?”

Sparkling drinks have long been popular.  I did not know, for example, that 12 liters of CO2 is dissolved in a pressurized bottle of champagne.  He talks about the smell of the product being increased 10 fold from the microexplosions as the bubbles pop.  There’s reference to the mustard receptor that suggests there’s a pain response.  Taste is made acidic by the production of hydrogen ions.  Ultimately, the “bubbly” engages all five senses, and that’s what grabs us!  Salud!  Cin Cin!  L’Chiam!

FROM MEDSCAPE UK / ANNE-GAËLLE MOULUN

Our Brain Loves Bubbles: CO2 Stimulates All Five Senses

In a video published on the Pasteur Institute website on January 2, neuroscientist Gabriel Lepousez, from the Perception and Memory Unit, explores the question: “Why does our brain love bubbles?”

Lepousez studied olfactory sensory perception and its health implications, particularly mental health and body-brain communication. While he does not focus exclusively on CO2, he acknowledges its role as an olfactory stimulus.

“It is one of many sensory stimuli, but not the subject of specific research,” he explained. However, inspired by the sparkling drinks that take centre stage during end-of-year celebrations, he decided to share insights into the neuroscience of bubbles.

Bubble Formation

The effervescence in sparkling drinks results from dissolved CO2; however, their formation also depends on external factors.

“In a pressurized bottle, such as champagne, 12 L of CO₂ remain dissolved. But once the bottle is opened and pressure decreases, the gas returns to its gaseous form, creating bubbles in the glass,” Lepousez explained.

“Interestingly, bubble formation is triggered by impurities on the glass surface, such as dust, microfibres, and microcracks, which serve as points of nucleation and formation of bubble columns. If you poured a carbonated drink into a perfectly clean, smooth glass, you might see no bubbles at all,” he emphasised.

“The magic of these drinks lies in the ability of CO2 to engage all five senses,” he said. “The bubbles capture our attention as they animate the liquid, making it appear alive and dynamic — unlike a still, flat drink. They also stimulate our hearing — the pop of a champagne cork, the hiss of a can opening, and the fizzing sound of bubbles rising in the glass all contribute to the sensory experience,” noted Lepousez.

Sensory Stimulation

Bubbles do more than just provide a captivating sight and sound. “Bubbles also stimulate our noses because each time a bubble finishes rising and bursts on the surface of the drink, its explosion triggers the projection of micro-aerosols into the air, which, like a mist, actively spray micro-droplets of perfumed liquid towards our nostrils and increasing 10-fold the vaporisation of odours in the air. This excess sensory stimulation directly activates our brain and increases the 10-fold intensity felt, which can be observed in functional brain imaging of a taster,” Lepousez explained.

CO2 is also an irritant gas that stimulates the same receptors as mustard. He noted, “That’s why it stings.”

The transient receptor potential ankyrin 1 receptor, commonly known as the mustard receptor, detects irritant compounds and plays a role in pain and inflammation. In the mouth, it is strongly expressed in the nerve endings of the trigeminal nerve, which innervates the oral and nasal cavities.

When exposed to a CO2-rich solution, these nerve endings are activated and transmit pain signals to the brain. This phenomenon can be studied in vitro using neuronal cultures, allowing precise control over molecular interactions and direct recording of their effects.

Taste and Texture

Bubbles also contribute to texture, creating a foam that adds thickness between the tongue and the palate. In addition, CO2 activates acid-detecting cells in the tongue.

“Does sparkling water taste more acidic and refreshing than still water? This is due to a chemical reaction between CO2 and water on the surface of our taste buds, producing hydrogen ions that trigger a mild acidic flavour. The simple CO2 molecule is unique in its ability to act on our five senses: Olfactory, gustatory, tactile, visual, and auditory — a true multisensory enhancer,” Lepousez concluded.

Source: https://www.medscape.com/viewarticle/our-b...

Slow Alzheimer's? You got it -- Get MOVING!

Here’s a quick take on a study from France and Monaco.  Folks over 70 were recruited from “memory centers” with complaints of memory issues, slow walking speed and issues with activities of daily living.  They were excluded if they were more restricted, or had dementia.  P-tau181, a known marker for Alzheimer’s was measured over time, as well as assessing physical activity and cognitive scores.  Even low levels of moderate to vigorous physical activity showed slower increases in the biomarker, though if the patients started with higher levels of p-tau181 there was no clear association.  

Don’t wait until things start going south – GET MOVING NOW!

FROM MEDPAGE UK / EDITED BY ANUSHREE CHAPHALKAR

Physical Activity May Slow Alzheimer's Pathology

— Lower risk of all-cause and cardiovascular mortality observed only among morning drinkers

TOPLINE:

Increased levels of moderate to vigorous physical activity were associated with a delayed rise in the concentration of phosphorylated tau181 (p-tau181) in blood over time in older adults with memory complaints, a study found. The cognitive benefits were attenuated at elevated baseline p-tau181 concentrations.

METHODOLOGY:

  • This post hoc secondary analysis of the MAPT trial included 558 adults with memory complaints aged 70 years or older, recruited from 13 memory centres in France and Monaco between 2008 and 2011.

  • Participants were eligible if they had spontaneous memory complaints, a gait speed ≤ 0.77 m/s, or a limitation in instrumental activities of daily living. Individuals with a diagnosis of dementia, Mini Mental State Examination scores < 24, or limitations in basic activities were excluded.

  • Concentrations of p-tau181 in blood were measured at baseline, 3 years, or both, and self-reported moderate to vigorous physical activity and cognitive composite scores were assessed at baseline, 6 months, and 1, 2, and 3 years.

TAKEAWAY:

  • Compared with inactive individuals, those with low or high levels of moderate to vigorous physical activity showed a slower increase in p-tau181 concentrations over time (regression coefficient [β], −0.109; P = .028 for low activity × time; β, −0.114; P = .018 for high activity × time).

  • Physical activity was not positively associated with cognitive composite scores when baseline p-tau181 concentrations exceeded 9.36 pg/mL for cross-sectional association and 3.5 pg/mL for longitudinal association.

  • No association was found between baseline concentrations of p-tau181 and baseline levels of moderate to vigorous physical activity.

IN PRACTICE:

"These findings support the current recommendation of increasing physical activity as a preventive tool against neurodegeneration, but further investigations are needed," the authors wrote.

SOURCE:

The study was led by Jérémy Raffin, PhD, Institut du Vieillissement, Gérontopôle de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France. It was published online on February 24 in The Lancet Healthy Longevity.

LIMITATIONS:

The study was limited by the use of subjective tools for assessing physical activity levels, which are prone to recall and response biases. Light-intensity physical activity was not considered and data on sedentary time were not collected. The study population was limited to adults aged 70 years or older, reducing generalisability. The assessment of education may not have fully captured variability. Additionally, factors such as fasting status were not controlled for, and the statistical analyses may have been influenced by missing confounder data and unmeasured confounding.

DISCLOSURES:

The study was supported by grants from Toulouse Gérontopôle, the French Ministry of Health, and the Pierre Fabre Research Institute. One author reported receiving multiple research grants, consulting for pharmaceutical and diagnostic companies, contributing to educational programs, and co-founding a biomarker company. Details are provided in the original article.

Source: https://www.medscape.com/viewarticle/physi...

Are We Going to Talk about Coffee Again? Yup!

I’m virtually certain you heard about this one – morning coffee saves lives, but not in the afternoon – or something like that!  

It’s been up and down for coffee, but really it’s a solid yes for everyone who doesn’t hate it or have a negative reaction to it.  So what’s new with this one?   Honestly, not much.  Years ago I wrote about how the more coffee you drank the longer you lived (ok, there’s a bit more to it than that), so long as you didn’t have an addictive personality.  That’s kind of what this says – if you drink coffee all day, you’re probably doing other things that will kill you sooner, so the coffee is “diluted”.

Recommendation --- 1 to 3 cups in the morning is fine.  Realize that the benefits come from the flavonoids and phytochemicals, not from caffeine.  Essentially, if you start pushing your caffeine into the afternoon, you might be looking for trouble, effecting sleep quality.  If you avoid that, knock yourself out.  

I personally like a decaf espresso at lunch (I know, it seems like you’re defeating the purpose, but at least it’s not like grandma’s decaf!)

Alla Salute!

FROM MEDPAGE TODAY / BY NICOLE LU

Coffee Drinking Tied to Better Survival, but Timing Matters

— Lower risk of all-cause and cardiovascular mortality observed only among morning drinkers

Key Takeaways

  • Lower risks of all-cause mortality and cardiovascular mortality were observed in people who mostly drank coffee in the morning.

  • Study is consistent with other literature showing an inverse association between moderate coffee consumption and mortality risk.

  • Definitive long-term trials to validate the present study findings deemed unlikely.

Any presumed health benefits of coffee may be limited to morning cups of joe, according to an observational study based on the National Health and Nutrition Examination Survey (NHANES).

Compared with non-coffee drinkers, those who mostly drank coffee in the morning had a lower risk of all-cause mortality (adjusted HR 0.84, 95% CI 0.74-0.95) and cardiovascular mortality (HR 0.69, 95% CI 0.55-0.87) when followed over a median 9.8 years.

It appeared that survival was particularly improved with morning consumers drinking moderate (>1 to 2 cups and >2 to 3 cups/day) and heavy (>3 cups/day) amounts of coffee rather than lesser amounts, reported Lu Qi, MD, PhD, epidemiologist of Tulane University in New Orleans and Harvard T.H. Chan School of Public Health in Boston, and colleagues in European Heart Journalopens in a new tab or window.

In contrast, people who kept drinking coffee later in the day, the all-day type, had no reduction in all-cause mortality (HR 0.96, 95% CI 0.83-1.12) and cardiovascular mortality (HR 0.82, 95% CI 0.61-1.10) regardless of how much they consumed.

Neither coffee drinking pattern was tied to more or less cancer-specific mortality.

"We found that coffee drinking timing was associated with all-cause mortality risk and [cardiovascular disease]-specific mortality risk independent of the amounts of coffee intake," Qi's group concluded. "Our findings highlight the importance of considering drinking timing in the association between the amounts of coffee intake and health outcomes."

The authors suggested two potential mechanisms that could explain their findings. One is that all-day caffeine consumption can disrupt circadian rhythms. Secondly, there may be anti-inflammatory substances within coffee that can counteract the body's pro-inflammatory cytokines when they are typically at their highest levels in the morning.

"Why would time of the day matter? In the morning hours there is commonly a marked increase in sympathetic activity as we wake up and get out of bed, an effect that fades away during the day and reaches its lowest level during sleep. Thus, it is possible, as the authors point out, that coffee drinking in the afternoon or evening disrupts the circadian rhythm of sympathetic activity," agreed Thomas Lüscher, MD, cardiologist of Royal Brompton and Harefield Hospitals in London and the University of Zurich, writing in an accompanying editorialopens in a new tab or window.

Previously, multiple observational studies had shown that moderate coffee consumptionopens in a new tab or window has an inverse association with mortality risk and risk of type 2 diabetes and other chronic conditions. At the same time, the data are mixed regarding heavy coffee consumption.

None of the work so far can establish causal relationships between coffee drinking and survival.

"We don't typically give advice about timing in our dietary guidance, but perhaps we should be thinking about this in the future," Qi nevertheless said in a press release. "Further studies are needed to validate our findings in other populations, and we need clinical trials to test the potential impact of changing the time of day when people drink coffee."

That may be easier said than done, however. "[T]hese cohorts are not randomized trials, probably as nobody wanted to be in the placebo group ... Be that as it may, it is unlikely that we will see a large, randomized trial over prolonged periods of time," Lüscher wrote.

"Overall, we must accept the now substantial evidence that coffee drinking, particularly in the morning hours, is likely to be healthy," he urged. "Thus, drink your coffee, but do so in the morning!"

Qi and colleagues performed their study using the 1999-2018 cycles of NHANES, a nationally representative cohort that includes health exams and lab tests. There were 40,725 adult participants identified who had completed 24-hour dietary recalls.

Reported coffee habits were fed into a cluster analysis that split participants into morning type (36%) and all-day types (16%) of coffee drinkers, the remainder considered non-coffee drinkers. These coffee drinking patterns were validated in 1,463 adults from the Women's and Men's Lifestyle Validation Study who had complete data on 7-day dietary records.

Compared with non-coffee drinkers, the morning and all-day types were older, more likely to be white, had higher family income, and a higher prevalence of diabetes, hypertension, and high cholesterol. Among coffee drinkers, the morning-type pattern was associated with more tea and caffeinated soda drinking but lower overall quantities of coffee than the all-day pattern.

The authors tried to adjust their mortality analyses to account for between-group differences in caffeinated and decaffeinated coffee intake amounts, sleep hours, and other confounders.

"Indeed, it is possible that coffee drinkers differ from non-drinkers in many aspects," Lüscher cautioned. "Of note, dietary and lifestyle habits, in particular smoking, may affect any of the observed associations. Some may work against the hypothesis provided in the current study as coffee drinkers are more likely to smoke than non-drinkers. This may particularly be the case of all-day drinkers who may be somewhat more addicted to this habit that may annihilate the protective effects of coffee drinking."

Other limitations to the study include the possibility of recall bias and measurement errors. Whether the findings can be generalized to other countries and other cultures is unknown.

Source: https://www.medpagetoday.com/primarycare/d...

Insulin Pumps and the World Traveler - Public Service Announcement

More and more people are becoming diabetic, and consequently more people are ending up using insulin pumps.  The technology is now fantastic and even type 1 diabetics whose sugars have been all over the place are now controlled.  But those people have realized that traveling wreaks havoc with glucose control.  Now we know why – BUBBLES!  For most people it’s not a big deal, but for some, it can be.  

Please forward this to anyone you know who uses an insulin pump.  They’ll find it useful.

FROM MEDSCAPE / BY MIRIAM E. TUCKER

Air Travel Alters Insulin Pump Delivery on Takeoff, Landing

MADRID — Airplane travel consistently causes insulin pumps to over-deliver a little over half a unit on takeoff and under-deliver a bit less on landing, new research found.

This phenomenon is due to air bubble formation and reabsorption in the insulin caused by ambient pressure changes in the airplane's cabin. It has nothing to do with the pump itself and happens with all insulin pumps, including those in hybrid closed-loop systems, Bruce King, MD, said at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

The extent to which this affects people with diabetes who use insulin pumps depends on their dose and insulin sensitivity among other factors, but all who fly should be aware of the possibility and take precautions, particularly with children, King, a pediatric endocrinologist at John Hunter Children's Hospital, Newcastle, Australia, told Medscape Medical News.

"Basically, the pumps are very safe in flight, but they deliver a little bit of extra insulin when you go up and stop delivery when you come back down again. There are a couple of simple steps that people can take to make sure that they don't have problems during the flight," he said.

Specifically, he advised that for pumps with tubing, wearers can disconnect just prior to takeoff and reconnect when the plane reaches cruising altitude, about 20 minutes into the flight. The insulin will still come out, but it won't be delivered to the person, King said.

On descent, they can disconnect after landing and prime the line to remove the insulin deficit.

With the Omnipod, which can't be disconnected, the only solution is to eat a small snack on takeoff. And on landing, eat another small snack such as a banana, and give a bolus for it to overcome the blockage of insulin delivery.

In any case, King said, "One of the most important things is informing people with diabetes about this effect so they're aware of it and can act appropriately when they fly."

Asked to comment, Nicholas B. Argento, MD, a practicing endocrinologist in Columbia, Maryland, and author of the American Diabetes Association's book Putting Your Patients on the Pump, called the issue a "minor effect," adding, "While I think it would be reasonable to make those changes…it seems like a lot of effort for a difference of 0.6 units extra on ascent and 0.5 units less on descent."

He noted there is a risk that the individual might forget to reattach the pump after 20 minutes, leading to hyperglycemia and even diabetic ketoacidosis. Instead, "one could put the pump on suspend for 1 hour on ascent. That would not stop the extra insulin but would net less insulin during that time period."

And after descent, "you have to walk a lot in most cases, so I don't think they need to take this into consideration. So many other factors change in air travel that I don't think this is a significant enough effect to make the effort."

A Known Phenomenon, the Manufacturers Are Aware

This phenomenon has been described previously, including by King in a 2011 Diabetes Care paper. The new research is among a series of experiments funded by the European Union Aviation Safety Agency in collaboration with the pump manufacturers Medtronic (MiniMed), Tandem (t:slim), and Insulet (Omnipod), primarily aimed at establishing safety parameters for airline pilots with insulin-treated diabetes.

Both the Omnipod DASH and Omnipod 5 User Guides include warnings about unintended insulin delivery during flight, and both advise users to check their blood glucose levels frequently while flying.

In a statement, Jordan Pinsker, MD, Chief Medical Officer at Tandem Diabetes Care, told Medscape Medical News, "While it has long been known that routine air travel pressure changes can cause minor fluctuations in insulin pump delivery, the impact of these variations have been found to be generally minor as it relates to glycemic control."

Pinsker added that the Tandem Mobi user manual includes a warning related to significant pressure changes in specific air travel situations and offers guidance to disconnect. However, "the t:slim X2 pump's microdelivery technology limits how much extra insulin can get delivered from air pressure changes due to a mechanism between the tubing and the contents of the bag inside the cartridge."

Medtronic's user guide says that the 780G system has not been tested at altitudes higher than 10,150 feet.

Hypobaric Chamber Used to Simulate Flight

The study was conducted in vitro, in a hypobaric chamber designed to mimic atmospheric changes during commercial flight. A total of 10 Medtronic MiniMed 780G, 10 Tandem t:slim X2, and six Insulet Omnipod DASH pumps were tested.

The hypobaric chamber was depressurized to 550 mm Hg over a 20-minute ascent, maintained at a 30-minute cruise, followed by a 20-minute descent to ground (750 mm Hg). During the simulated flights, insulin infusion was set at 0.6 units per hour, a rate typical for both adults and children, to allow accurate measurements with multiple flights.

Insulin delivery rates and bubble formation were recorded by attaching infusion sets to open-ended 100 µL capillary tubes against 1-mm grid paper.

Full cartridges — Medtronic: 3 mL, t:slim: 3 mL, and Omnipod: 2 mL — all over-delivered 0.60 units of insulin over a 20-minute ascent compared with delivery at ground level. And during descent, the cartridges under-delivered 0.51 units of insulin.

But if There's Rapid Decompression…

In a separate protocol, insulin infusion sets without pumps were tested in a simulation of rapid decompression. Insulin delivery during both ascent and descent showed statistically significant differences compared with delivery at ground level (both P < .001). In this scenario, fluid delivery was equivalent to 5.6 units of excess insulin.

King pointed out that while these are rare events, about 40-50 occur annually. One was the widely publicized Alaska Airlines flight in January 2024 when the door fell off in midair.

Argento commented, "The catastrophic decompression is of note, and I would want patients to be aware of this, but it is asking a lot for someone thinking they are going to die to remember to disconnect as it starts."

The researchers are investigating this phenomenon further in people, including airline pilots.

Source: https://www.medscape.com/viewarticle/air-t...

Depression and Ice Cream

Headlines often conflate associations into causation, essentially as click-bait.  What does that mean?  

My favorite example is “Ice Cream Causes Drowning”.  No – I don’t mean the kids went swimming too soon after eating (that’s a myth, too, by the way).  Drowning increases when more people go swimming.  More people go swimming when it’s hot; more people eat ice cream when it’s hot, ergo – ice cream causes drowning.  Duh --- NO!  Association is not causation.

Here we have more steps equals less depression.  But how do we know that the more depressed on is, the less likely they are to walk lots of steps?  Meta-analyses group together lots of studies that may look at different questions, but have data that can be examined from a different angle.  Opportunities to point to causation is extremely limited.  Most of the articles these days are in this category, so be careful in the conclusions you draw.

What can we say?  If you walk more, you’re less likely to be depressed.  Does walking more decrease depressive symptoms?  The answer to that is YES – just not from this meta-analysis.

FROM MEDSCAPE / BY ANUSHREE CHAPHALKAR

Can Walking More Steps Per Day Help Keep Depression Away?

TOPLINE:

Walking 7000 or more steps per day is associated with fewer depressive symptoms and a 31% lower risk for depression than taking fewer steps, a new meta-analysis shows.

METHODOLOGY:

  • Researchers conducted a systematic review and meta-analysis of 33 observational studies that included more than 96,000 adults aged 18-91 years.

  • Data were obtained from 27 cross-sectional and 6 longitudinal studies and from 5 major databases through May 2024.

  • Objectively measured daily step counts and depression data were collected via various assessment tools.

TAKEAWAY:

  • The number of daily steps had a significant inverse correlation with depressive symptoms in both cross-sectional (correlation coefficient [r], −0.12; 95% CI, −0.20 to −0.04) and panel studies (r, −0.17; 95% CI, −0.28 to −0.04).

  • Participants achieving 7000 steps per day or more showed a lower risk for depression than those achieving less than 7000 steps per day (risk ratio [RR], 0.69; 95% CI, 0.62-0.77).

  • An additional increase of 1000 steps per day was associated with a 9% lower risk for depression (RR, 0.91; 95% CI, 0.87-0.94).

  • Cross-sectional analysis showed that, compared with walking less than 5000 steps per day, walking 5000-7499 steps per day, 7500-9999 steps per day, and at least 10,000 steps per day were all significantly associated with fewer depressive symptoms (standardized mean difference, −0.17, −0.27, and −0.26, respectively).

IN PRACTICE:

"The objective measurement of daily steps may represent an inclusive and comprehensive approach to public health that has the potential to prevent depression. Small amounts of PA [physical activity] may be particularly relevant for specific populations, such as older adults and individuals with limited activities of daily living, for whom daily steps emerge as an accessible PA strategy," the investigators wrote.

SOURCE:

The study was led by Bruno Bizzozero-Peroni, PhD, Health and Social Research Center, Universidad de Castilla-La Mancha, Cuenca, Spain. It was published online December 16 in JAMA Network Open.

LIMITATIONS:

Reverse associations were possible, and causal inferences could not be made from the findings. In addition, the analysis showed substantial between-study heterogeneity in some pooled estimates, partially explained by differences in participant characteristics and step-counting devices. Most studies also lacked robust methods, potentially affecting result reliability, and the meta-analysis comparing high vs low daily step counts may have been susceptible to publication bias.

DISCLOSURES:

The study was funded by the University of Castilla-La Mancha, National Agency for Research and Innovation, Ministry of Economy and Competitiveness of Spain, Carlos III Health Institute, European Regional Development Fund, and European Union's Next Generation EU initiative. No conflicts of interest were reported.

Source: https://www.medscape.com/viewarticle/can-w...